Antisense vimentin cDNA combined with chondroitinase ABC reduces glial scar and cystic cavity formation following spinal cord injury in rats.
The formation of glial scar and cystic cavities restricts axon regeneration after spinal cord injury. Chondroitin sulphate proteoglycans (CSPGs) are regarded as the prominent inhibitory molecules in the glial scar, and their inhibitory effects may be abolished in part by chondroitinase ABC (ChABC), which can digest CSPGs. CSPGs are secreted mostly by reactive astrocytes, which form dense scar tissues. The intermediate filament protein vimentin underpins the cytoskeleton of reactive astrocytes. Previously we have shown that retroviruses carrying full-length antisense vimentin cDNA reduce reactive gliosis. Here we administered both antisense vimentin cDNA and ChABC to hemisected rat spinal cords. Using RT-PCR, Western blotting and immunohistochemistry, we found that the combined treatment reduced the formation of glial scar and cystic cavities through degrading CSPGs molecules and inhibiting intermediate filament proteins. The modified intra- and extra-cellular architecture may alter the physical and biochemical characteristics of the scar, and the combined therapy might be used to inhibit glial scar formation.
Xia
Yongzhi
Y
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Zhao
Tianzhi
T
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Li
Jian
J
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Li
Lan
L
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Hu
Rong
R
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Hu
Shengli
S
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China.
Feng
Hua
H
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China. Electronic address: fhnwk@yahoo.com.cn.
Lin
Jiangkai
J
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Gaotanyan 30, Chongqing 400038, China. Electronic address: jklin2002@yahoo.com.cn.
D000818:Animals; D019765:Chondroitin ABC Lyase / Q000008:administration & dosage*; D002809:Chondroitin Sulfates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D002921:Cicatrix / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D003560:Cysts / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016373:DNA, Antisense / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D015316:Genetic Therapy; D009416:Nerve Regeneration / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology; D013119:Spinal Cord Injuries / Q000150:complications / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D014746:Vimentin / Q000037:antagonists & inhibitors* / Q000235:genetics
D016373:DNA, Antisense; D018076:DNA, Complementary; D014746:Vimentin; D002809:Chondroitin Sulfates; D019765:Chondroitin ABC Lyase